Summary: A critical component of a biologics license application is the description of the validation of analytical methods and the establishment of specifications for the product subject of the application and its intermediates obtained during manufacturing. The Laboratory of Methods Development and Quality Control (LMDQC) is a resource of the Division of Bacterial, Parasitic and Allergenic Products (DBPAP). LMDQC works with other laboratories within DBPAP and with the sponsor to ensure the timely development of standardized tests for the quality assessment of bacterial products. Additionally, during the methods development process, needs for reference materials are identified and production and standardization of materials is coordinated. FY2002 activities: Clinical evaluations of the efficacy of diphtheria toxoid vaccines are based on measurement of the toxin-neutralizing serum antibodies. Investigation of the Vero cell culture method, an assay commonly used to measure diphtheria toxin-neutralizing antibodies in human sera, continued in an effort to improve standardization. In addition, toxin-neutralizing antibodies are being measured in sera of guinea pig immunized with diphtheria toxoid vaccines using a Vero cell assay using low amounts of toxin and an in vivo guinea-pig skin neutralization (Lr) test. In order to determine the best alternative to the current lethal challenge test, the results from these 2 assays are being compared to each other, the routine challenge test in guinea pigs, and a high-dose Vero cell assay performed by CBER's Laboratory of Standards and Testing.